法国图卢兹大学Elsa Suberbielle小组近日取得一项新成果。经过不懈努力，他们研究出弓形虫感染和慢性IL-1升高驱动海马DNA双链断裂信号，导致认知缺陷。该项研究成果发表在2025年8月21日出版的《自然—神经科学》上。

本研究表明，长期感染弓形虫的小鼠表现出空间记忆受损，这依赖于神经元IL-1信号传导，并通过长期暴露于IL-1β来模拟。弓形虫感染和慢性IL-1β均驱动H2A。海马神经元中X依赖的DNA双链断裂信号和神经元H2A的失效。依赖于X的信号阻断了由任何一种暴露引起的记忆损伤。他们的研究结果强调了细胞因子诱导的双链断裂依赖信号在空间记忆缺陷中的重要作用，这可能与多种脑部疾病有关。

据介绍，由感染引起的慢性炎症，其特征是白细胞介素-1（IL-1）等细胞因子水平升高，但对于IL-1如何通过表观遗传过程导致认知障碍知之甚少。

附：英文原文

Title: Toxoplasma gondii infection and chronic IL-1 elevation drive hippocampal DNA double-strand break signaling, leading to cognitive deficits

Author: Belloy, Marcy, Schmitt, Benjamin A. M., Marty, Florent H., Paut, Charlotte, Bassot, Emilie, Ada, Amel, Alis, Marine, Zahm, Margot, Chaubet, Adeline, Garnier, Hugo, Flores-Aguilar, Thelma, Roitg, Elisa, Gutierrez-Loli, Renzo, Allart, Sophie, Ecalard, Romain, Boursereau, Raphal, Ligat, Gatan, Gonzalez-Dunia, Daniel, Blanchard, Nicolas, Suberbielle, Elsa

Issue&Volume: 2025-08-21

Abstract: Chronic inflammation, resulting from infections, is characterized by increased levels of cytokines including interleukin-1 (IL-1), but little is known about how IL-1 contributes to cognitive impairment, potentially via epigenetic processes. Here we demonstrate that mice chronically infected with the parasite Toxoplasma gondii exhibit impaired spatial memory, which is dependent on neuronal IL-1 signaling and mimicked by chronic exposure to IL-1β. Both T. gondii infection and chronic IL-1β drive H2A.X-dependent DNA double-strand break signaling in hippocampal neurons and invalidating neuronal H2A.X-dependent signaling blocks memory impairments caused by either exposure. Our results highlight the instrumental role of cytokine-induced double-strand-break-dependent signaling in spatial memory defects, which may be relevant to multiple brain diseases.

DOI: 10.1038/s41593-025-02041-x

Source: https://www.nature.com/articles/s41593-025-02041-x